1. Field of the Invention
This invention relates to compounds for use in 3 and 4 component condensation reactions. The invention also relates to methods for synthesizing cyclic derivatives by the 3 and 4 component condensation reaction.
2. Description of the Related Art
The multi-component reaction (MCR) is a useful process for preparing large arrays of diverse compounds. In a typical multi-component reaction, three or more starting materials are reacted with one another simultaneously or almost simultaneously in a one-pot reaction. The process does not require the work up of intermediates.
Multi-component reactions in which one of the components is an isocyanide include the Passerini 3-component reaction (P-3CR); the Ugi 4-component reaction (U-4CR) [I. Ugi, Angew. Chem. 1962, 74, 9]; and the Ugi 4-component reaction with β-amino acids (U-4CR/β-AS) [I. Ugi et al., Tetrahedron 1995, 51, 139].
The Ugi/De-BOC/Cyclization (UDC) strategy has been employed in combination with isocyano compounds in a solution phase synthesis of constrained Ugi derivatives (Hulme et al., Tetrahedron Lett. 1998, 39, 1113). Conversion of Ugi products derived from (β-isocyano-ethyl)-alkyl carbonates to N-acylated α-amino acids and esters has been reported (Ugi et al., Tetrahedron, 1999, 55, 7411). The solution techniques are not resin bound and are therefore not useful for high speed synthesis because of purity problems. The solution/solid phase generation of γ-lactam analogs has also been reported. This procedure tethers N-BOC aldehydes of an Ugi multi-component reaction to a solid support. BOC removal and treatment with base affords γ-lactams. (Hulme et al., Tetrahedron Lett. 2000, 41, 1883). This method suffers in that it results in the formation of primary amide by-products.
Cyclic derivatives, such as diketopiperazine and diketobenzodiazepine ring systems, are found in a wide variety of compounds having diverse medicinal utility. Based upon the usefulness of these compounds, it would generally be advantageous to have structures and methods of rapidly and efficiently synthesizing structurally diverse derivatives of these and other cyclic compounds, as well as libraries containing large numbers of such compounds. The present invention meets these and other needs.